The overall objective of the proposed research is to investigate the neurochemical mechanism by which the ovarian hormones, estradiol and progesterone control the secretion of luteinizing hormone (LH) from the pituitary gland. This research will test the hypothesis that the ovarian hormones control LH release by altering the activity of the monoamine neurotransmitters, norepinephrine, dopamine, and serotonin, that innervate specific nuclei of the hypothalamus and limbic system. This hypothesis will be tested by two experimental approaches. First, experiments will measure the turnover rates of the monoamines in individual brain nuclei after administration of estradiol and progesterone to ovariectomized rats in regimes that stimulate or suppress the release of LH. Plasma concentrations of LH, determined by radioimmunoassay, will be correlated with the turnover rates of the monoamines after each hormonal treatment. This procedure is designed to identify discrete sites where ovarian hormones affect neurotransmitter activity. The second phase of the research will establish whether causal relationship exist between the change in neurotransmitter activity and the secretion of LH. These experiments will test whether it is possible to alter the expected hormonal feedback effect on LH release by selectively denervating the monoaminergic input to specific brain nuclei with intracerebral micro-injections of the monoamine neurotoxins, 6-hydroxydopamine and 5,7-dihydroxytryptamine. If these neurochemical lesions influence the hormonal effect on LH secretion, this would be evidence that specific neurotransmitter systems mediate each feedback process.